Theranostics
2021; 11(17):8337-8349.
doi:10.7150/thno.62686 This issueCite
Review
Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins
Jiayi Lin1*, Jinmei Jin1*, Yiwen Shen1*, Lijun Zhang1, Gang Gong1, Huiting Bian1, Hongzhuan Chen1, Dale G. Nagle3, Ye Wu1✉, Weidong Zhang1,2✉, Xin Luan1✉
1. Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China 2. School of Pharmacy, Second Military Medical University, Shanghai, 201203, China 3. Department of Biomolecular Sciences and Research of Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677-1848, USA *These authors contributed equally to this work.
✉ Corresponding authors: Dr. Ye Wu, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; orcid.org/0000-0003-4974-0774; Email: wuye@shutcm.edu.cn. Prof. Weidong Zhang, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Second Military Medical University, Shanghai, 201203, China; orcid.org/0000-0002-7384-2490; Email: dzhangy@hotmail.com. Prof. Xin Luan, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; orcid.org/0000-0003-3674-256X; Email: luanxin@shutcm.edu.cn.More
Citation:
Lin J, Jin J, Shen Y, Zhang L, Gong G, Bian H, Chen H, Nagle DG, Wu Y, Zhang W, Luan X. Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins. Theranostics 2021; 11(17):8337-8349. doi:10.7150/thno.62686. https://www.thno.org/v11p8337.htm
Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the accessible binding sites to achieve prolonged occupancy and influence protein functions. The emerging targeted protein degradation (TPD) strategies exemplified by PROteolysis TArgeting Chimeras (PROTACs) are revolutionizing conventional drug discovery modality to target proteins of interest (POIs) that were categorized as “undruggable” before, however, these strategies are limited within intracellular POIs. The novel new degrader technologies such as LYsosome-TArgeting Chimaeras (LYTACs) and Antibody-based PROTACs (AbTACs) have been successfully developed to expand the scope of TPD to extracellular and membrane proteins, fulfilling huge unmet medical needs. Here, we systematically review the currently viable protein degradation strategies, emphasize that LYTACs and AbTACs turn a new avenue for the development of TPD, and highlight the potential challenges and directions in this vibrant field.
Keywords: targeted protein degradation (TPD), extracellular and membrane proteins, LYTAC, AbTAC
Citation styles
APA
Lin, J., Jin, J., Shen, Y., Zhang, L., Gong, G., Bian, H., Chen, H., Nagle, D.G., Wu, Y., Zhang, W., Luan, X. (2021). Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins. Theranostics, 11(17), 8337-8349. https://doi.org/10.7150/thno.62686.
Lin J, Jin J, Shen Y, Zhang L, Gong G, Bian H, Chen H, Nagle DG, Wu Y, Zhang W, Luan X. Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins. Theranostics 2021; 11(17):8337-8349. doi:10.7150/thno.62686. https://www.thno.org/v11p8337.htm
CSE
Lin J, Jin J, Shen Y, Zhang L, Gong G, Bian H, Chen H, Nagle DG, Wu Y, Zhang W, Luan X. 2021. Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins. Theranostics. 11(17):8337-8349.
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